DESCRIPTION: Many leukemias and lymphomas are strongly associated with non-random chromosomal translocations. Many of the most intensely studied translocations have been proven to be causal events in the development of leukemias. The molecular events resulting in these translocations have not been well characterized and are the focus of this application. The first specific aim seeks to characterize site-specific double strand DNA cleavage within the MLL locus induced by topo II inhibitors. The second aim seeks to characterize site-specific DNA cleavage induced by topo II inhibitors in two additional loci AML-1 and RARA. The third aim is to develop a general in vitro model system of topo II inhibitor induced translocations and to identify regions of the genome prone to chromosomal translocations.